FDA approves oral decitabine/cedazuridine plus venetoclax for older AML patients unable to tolerate intensive chemo

The FDA has approved the oral combination of decitabine/cedazuridine (Inqovi) with venetoclax (Venclexta) for adults with newly diagnosed acute myeloid leukemia who are at least 75 years old or have comorbidities that make intensive chemotherapy unsuitable.

The approval is based on the phase 2 ASCERTAIN‑V part B trial, which administered decitabine/cedazuridine on days 1‑5 of a 28‑day cycle together with a venetoclax ramp‑up to 400 mg daily through day 28 for the first three cycles.

The study reported a complete remission rate of 46.5% and a combined CR/CRi rate of 63.4%. Among those achieving remission, 75.3% maintained response at 12 months, and median overall survival was 15.5 months after a median follow‑up of 11.2 months.

Patients were elderly and frail (median age 78) with a mix of risk categories and 16.8% carrying TP53 mutations. Grade ≥ 3 adverse events occurred in 98% of participants, mainly cytopenias and febrile neutropenia; treatment interruptions were seen in 68.3%, discontinuations in 8.9%, and fatal events in 15.8%.